Keratin 15, transcobalamin I and homeobox gene Hox-B13 expression in breast phyllodes tumors: novel markers in biological classification

Breast phyllodes tumors are rare neoplasms which present challenges for histological classification. Microscopic features are not always predictive of clinical behavior, and scarce data exist on the prognostic role of biological markers. Our study evaluated a series of 145 phyllodes tumors diagnosed...

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Veröffentlicht in:Breast cancer research and treatment 2012-02, Vol.132 (1), p.143-151
Hauptverfasser: Chong, Luke Yong-Zheng, Cheok, Poh Yian, Tan, Wai-Jin, Thike, Aye Aye, Allen, George, Ang, Mei Kim, Ooi, Aik Seng, Tan, Patrick, Teh, Bin Tean, Tan, Puay Hoon
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container_title Breast cancer research and treatment
container_volume 132
creator Chong, Luke Yong-Zheng
Cheok, Poh Yian
Tan, Wai-Jin
Thike, Aye Aye
Allen, George
Ang, Mei Kim
Ooi, Aik Seng
Tan, Patrick
Teh, Bin Tean
Tan, Puay Hoon
description Breast phyllodes tumors are rare neoplasms which present challenges for histological classification. Microscopic features are not always predictive of clinical behavior, and scarce data exist on the prognostic role of biological markers. Our study evaluated a series of 145 phyllodes tumors diagnosed at the Department of Pathology, Singapore General Hospital between 2006 and 2009, incorporating 91 (62.8%) benign, 40 (27.6%) borderline, and 14 (9.7%) malignant phyllodes tumors. Antibodies to keratin 15 (KRT15), transcobalamin I (TCN1), and homeobox gene Hox-B13 (HOXB13) were applied to sections cut from tissue microarray blocks. KRT15 and TCN1 positivity was defined when there was reactivity of 1% or more stromal cells, while HOXB13 positivity was defined using a H-score of 100 and above. Positive immunohistochemical expression for KRT15, TCN1, and HOXB13 was seen in 21 (14.5%), 96 (66.2%), and 66 (45.5%) of tumors, respectively. Stromal expression of KRT15, TCN1, and HOXB13 was significantly correlated with tumor grade ( P  
doi_str_mv 10.1007/s10549-011-1555-6
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Microscopic features are not always predictive of clinical behavior, and scarce data exist on the prognostic role of biological markers. Our study evaluated a series of 145 phyllodes tumors diagnosed at the Department of Pathology, Singapore General Hospital between 2006 and 2009, incorporating 91 (62.8%) benign, 40 (27.6%) borderline, and 14 (9.7%) malignant phyllodes tumors. Antibodies to keratin 15 (KRT15), transcobalamin I (TCN1), and homeobox gene Hox-B13 (HOXB13) were applied to sections cut from tissue microarray blocks. KRT15 and TCN1 positivity was defined when there was reactivity of 1% or more stromal cells, while HOXB13 positivity was defined using a H-score of 100 and above. Positive immunohistochemical expression for KRT15, TCN1, and HOXB13 was seen in 21 (14.5%), 96 (66.2%), and 66 (45.5%) of tumors, respectively. Stromal expression of KRT15, TCN1, and HOXB13 was significantly correlated with tumor grade ( P  &lt; 0.001, P  &lt; 0.001, P  = 0.012), stromal hypercellularity ( P  = 0.005, P  &lt; 0.001, P  = 0.023), mitotic activity ( P  &lt; 0.001), and microscopic borders ( P  = 0.006, P  &lt; 0.001, P  = 0.011). Co-expression of TCN1 and HOXB13 was seen in 21 of 91 (23.1%) benign, 18 of 40 (45.0%) borderline, and 11 of 14 (78.6%) malignant tumors, suggesting that the dual-marker panels of TCN1 and HOXB13 might be helpful in classifying borderline and malignant tumors. Although expression of TCN1 alone was present in all malignant and 34 of 40 (85.0%) borderline tumors, a combined panel with HOXB13 excluded some benign cases and was a better discriminant for a significant proportion of borderline and malignant tumors.</description><identifier>ISSN: 0167-6806</identifier><identifier>EISSN: 1573-7217</identifier><identifier>DOI: 10.1007/s10549-011-1555-6</identifier><identifier>PMID: 21574054</identifier><identifier>CODEN: BCTRD6</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Adolescent ; Adult ; Aged ; Analysis ; Biological and medical sciences ; Biomarkers ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Breast cancer ; Breast Neoplasms - classification ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Breasts ; Cancer research ; Cancer therapies ; Case-Control Studies ; Classification ; Diagnosis ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes ; Gynecology. 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Microscopic features are not always predictive of clinical behavior, and scarce data exist on the prognostic role of biological markers. Our study evaluated a series of 145 phyllodes tumors diagnosed at the Department of Pathology, Singapore General Hospital between 2006 and 2009, incorporating 91 (62.8%) benign, 40 (27.6%) borderline, and 14 (9.7%) malignant phyllodes tumors. Antibodies to keratin 15 (KRT15), transcobalamin I (TCN1), and homeobox gene Hox-B13 (HOXB13) were applied to sections cut from tissue microarray blocks. KRT15 and TCN1 positivity was defined when there was reactivity of 1% or more stromal cells, while HOXB13 positivity was defined using a H-score of 100 and above. Positive immunohistochemical expression for KRT15, TCN1, and HOXB13 was seen in 21 (14.5%), 96 (66.2%), and 66 (45.5%) of tumors, respectively. Stromal expression of KRT15, TCN1, and HOXB13 was significantly correlated with tumor grade ( P  &lt; 0.001, P  &lt; 0.001, P  = 0.012), stromal hypercellularity ( P  = 0.005, P  &lt; 0.001, P  = 0.023), mitotic activity ( P  &lt; 0.001), and microscopic borders ( P  = 0.006, P  &lt; 0.001, P  = 0.011). Co-expression of TCN1 and HOXB13 was seen in 21 of 91 (23.1%) benign, 18 of 40 (45.0%) borderline, and 11 of 14 (78.6%) malignant tumors, suggesting that the dual-marker panels of TCN1 and HOXB13 might be helpful in classifying borderline and malignant tumors. 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Microscopic features are not always predictive of clinical behavior, and scarce data exist on the prognostic role of biological markers. Our study evaluated a series of 145 phyllodes tumors diagnosed at the Department of Pathology, Singapore General Hospital between 2006 and 2009, incorporating 91 (62.8%) benign, 40 (27.6%) borderline, and 14 (9.7%) malignant phyllodes tumors. Antibodies to keratin 15 (KRT15), transcobalamin I (TCN1), and homeobox gene Hox-B13 (HOXB13) were applied to sections cut from tissue microarray blocks. KRT15 and TCN1 positivity was defined when there was reactivity of 1% or more stromal cells, while HOXB13 positivity was defined using a H-score of 100 and above. Positive immunohistochemical expression for KRT15, TCN1, and HOXB13 was seen in 21 (14.5%), 96 (66.2%), and 66 (45.5%) of tumors, respectively. Stromal expression of KRT15, TCN1, and HOXB13 was significantly correlated with tumor grade ( P  &lt; 0.001, P  &lt; 0.001, P  = 0.012), stromal hypercellularity ( P  = 0.005, P  &lt; 0.001, P  = 0.023), mitotic activity ( P  &lt; 0.001), and microscopic borders ( P  = 0.006, P  &lt; 0.001, P  = 0.011). Co-expression of TCN1 and HOXB13 was seen in 21 of 91 (23.1%) benign, 18 of 40 (45.0%) borderline, and 11 of 14 (78.6%) malignant tumors, suggesting that the dual-marker panels of TCN1 and HOXB13 might be helpful in classifying borderline and malignant tumors. Although expression of TCN1 alone was present in all malignant and 34 of 40 (85.0%) borderline tumors, a combined panel with HOXB13 excluded some benign cases and was a better discriminant for a significant proportion of borderline and malignant tumors.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>21574054</pmid><doi>10.1007/s10549-011-1555-6</doi><tpages>9</tpages></addata></record>
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subjects Adolescent
Adult
Aged
Analysis
Biological and medical sciences
Biomarkers
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Breast cancer
Breast Neoplasms - classification
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Breasts
Cancer research
Cancer therapies
Case-Control Studies
Classification
Diagnosis
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genes
Gynecology. Andrology. Obstetrics
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Humans
Keratin
Keratin-15 - genetics
Keratin-15 - metabolism
Mammary gland diseases
Medical sciences
Medicine
Medicine & Public Health
Microarray Analysis
Middle Aged
Oncology
Phyllodes Tumor - classification
Phyllodes Tumor - metabolism
Phyllodes Tumor - pathology
Preclinical Study
Tissue Array Analysis
Transcobalamins - genetics
Transcobalamins - metabolism
Tumors
Young Adult
title Keratin 15, transcobalamin I and homeobox gene Hox-B13 expression in breast phyllodes tumors: novel markers in biological classification
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